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Alcohol and glutamate

Ashley C Nelson, Stephanie B Williams, Stephanie S Pistorius, Hyun J Park, Taylor J Woodward, Andrew J Payne, J Daniel Obray, Samuel I Shin, Jennifer K Mabey, Scott C Steffensen
The neural mechanisms underlying alcohol dependence are not well-understood. GABAergic neurons in the ventral tegmental area (VTA) are a relevant target for ethanol. They are inhibited by ethanol at physiologically-relevant levels in vivo and display marked hyperexcitability during withdrawal. In the present study, we examined the effects of the GABA(A) receptor agonist muscimol on VTA neurons ex vivo following withdrawal from acute and chronic ethanol exposure. We used standard cell-attached mode electrophysiology in the slice preparation to evaluate the effects of muscimol on VTA GABA neuron firing rate following exposure to acute and chronic ethanol in male CD-1 GAD-67 GFP mice...
2018: Frontiers in Neuroscience
Stefan E Payer, Hannah Pollak, Silvia M Glueck, Kurt Faber
The promiscuous regio- and stereoselective hydration of 4-hydroxystyrenes catalyzed by ferulic acid decarboxylase from Enterobacter sp. (FDC_ Es ) depends on bicarbonate bound in the active site, which serves as a proton relay activating a water molecule for nucleophilic attack on a quinone methide electrophile. This "cofactor" is crucial for achieving improved conversions and high stereoselectivities for ( S )-configured benzylic alcohol products. Similar effects were observed with simple aliphatic carboxylic acids as additives...
March 2, 2018: ACS Catalysis
Anni I Lehikoinen, Olli K Kärkkäinen, Marko A S Lehtonen, Seppo O K Auriola, Kati J Hanhineva, Seppo T Heinonen
BACKGROUND: Although the effects of alcohol on metabolic processes in the body have been studied widely, there do not appear to be any previous reports clarifying how substance abuse changes metabolic profiles of pregnant women during the first trimester of pregnancy. OBJECTIVE: Our aim was to evaluate the effect of substance abuse, especially alcohol use, on the metabolic profile of pregnant women during the first trimester. STUDY DESIGN: We applied mass spectrometry based non-targeted metabolite profiling of serum collected during routine visit to the hospital between gestational weeks 9 + 0 to 11 + 6 from controls (n = 55), alcohol users (n = 19), drug users (n = 24) and tobacco smokers (n = 40)...
February 17, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Daniel Lindberg, Lindsey Andres-Beck, Yun-Fang Jia, Seungwoo Kang, Doo-Sup Choi
Alcohol use disorder (AUD) is a debilitating condition marked by cyclic patterns of craving, use, and withdrawal. These pathological behaviors are mediated by multiple neurotransmitter systems utilizing glutamate, GABA, dopamine, ATP, and adenosine. In particular, purines such as ATP and adenosine have been demonstrated to alter the phase and function of the circadian clock and are reciprocally regulated by the clock itself. Importantly, chronic ethanol intake has been demonstrated to disrupt the molecular circadian clock and is associated with altered circadian patterns of activity and sleep...
2018: Frontiers in Physiology
Verginia C Cuzon Carlson
Alcohol (ethanol) is a widely used and abused drug with approximately 90% of adults over the age of 18 consuming alcohol at some point in their lifetime. Alcohol exerts its actions through multiple neurotransmitter systems within the brain, most notably the GABAergic and glutamatergic systems. Alcohol's actions on GABAergic and glutamatergic neurotransmission have been suggested to underlie the acute behavioral effects of ethanol. The striatum is the primary input nucleus of the basal ganglia that plays a role in motor and reward systems...
February 20, 2018: Handbook of Experimental Pharmacology
Caroline E Germany, Ashlie N Reker, David J Hinton, Alfredo Oliveros, Xinggui Shen, Lindsey G Andres-Beck, Katheryn M Wininger, Marjan Trutchul, Urska Cvek, Doo-Sup Choi, Hyung W Nam
Acamprosate is an FDA-approved medication for the treatment of alcoholism that is unfortunately only effective in certain patients. Although acamprosate known to stabilize the hyper-glutamatergic state in alcoholism, pharmacological mechanisms of action in brain tissue remains unknown. To investigate the mechanism of acamprosate efficacy, we employed a pharmacoproteomics approach using an animal model of alcoholism, type 1 equilibrative nucleoside transporter (ENT1) null mice. Our results demonstrated that acamprosate treatment significantly decreased both ethanol drinking and preference in ENT1 null mice compared to that of wild-type mice...
February 13, 2018: Proteomics
Daniel F Hermens, Jim Lagopoulos
Binge drinking has significant effects on memory, particularly with regards to the transfer of information to long-term storage. Partial or complete blocking of memory formation is known as blackout. Youth represents a critical period in brain development that is particularly vulnerable to alcohol misuse. Animal models show that the adolescent brain is more vulnerable to the acute and chronic effects of alcohol compared with the adult brain. This mini-review addresses the neurobiological underpinnings of binge drinking and associated memory loss (blackout) in the adolescent and young adult period...
2018: Frontiers in Psychology
Laura Sánchez-Marín, David Ladrón de Guevara-Miranda, Mari Carmen Mañas-Padilla, Francisco Alén, Román D Moreno-Fernández, Caridad Díaz-Navarro, José Pérez-Del Palacio, María García-Fernández, Carmen Pedraza, Francisco J Pavón, Fernando Rodríguez de Fonseca, Luis J Santín, Antonia Serrano, Estela Castilla-Ortega
The systemic administration of lysophosphatidic acid (LPA) LPA1/3 receptor antagonists is a promising clinical tool for cancer, sclerosis and fibrosis-related diseases. Since LPA1 receptor-null mice engage in increased ethanol consumption, we evaluated the effects of systemic administration of an LPA1/3 receptor antagonist (intraperitoneal ki16425, 20 mg/kg) on ethanol-related behaviors as well as on brain and plasma correlates. Acute administration of ki16425 reduced motivation for ethanol but not for saccharine in ethanol self-administering Wistar rats...
January 26, 2018: Neuropharmacology
Carolina L Haass-Koffler, Kimberly Goodyear, Antonella Loche, Victoria M Long, Carla Lobina, Harrison H Tran, Roberto Cacciaglia, Robert M Swift, Giancarlo Colombo, Lorenzo Leggio
Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male volunteers ( n=14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice...
January 1, 2018: Journal of Psychopharmacology
Gil Leurquin-Sterk, Jenny Ceccarini, Cleo L Crunelle, Bart de Laat, Jef Verbeek, Stephanie Deman, Hugo Neels, Guy Bormans, Hendrik Peuskens, Koen Van Laere
Animal studies suggest an important role for the metabotropic glutamate receptor subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human evidence is lacking. The goal of this study was to investigate cerebral mGlu5 availability in alcohol-dependent patients versus controls using 18F-FPEB positron emission tomography. Methods: Dynamic 90 minute 18F-FPEB scans combined with arterial blood sampling were acquired in 16 recently abstinent alcohol-dependent patients and 32 age-matched controls...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Hu Cheng, Derek Kellar, Allison Lake, Peter Finn, George V Rebec, Shalmali Dharmadhikari, Ulrike Dydak, Sharlene Newman
Growing evidence suggests that glutamate neurotransmission plays a critical role in alcohol addiction. Cue-induced change of glutamate has been observed in animal studies but never been investigated in humans. This work investigates cue-induced change in forebrain glutamate in individuals with alcohol use disorder (AUD). A total of 35 subjects (17 individuals with AUD and 18 healthy controls) participated in this study. The glutamate concentration was measured with single-voxel 1H-MR spectroscopy at the dorsal anterior cingulate...
January 10, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Kaziya M Lee, Michal A Coelho, MacKayla A Class, Karen K Szumlinski
Binge alcohol-drinking elicits symptoms of negative affect such as anxiety upon cessation, which is a source of negative reinforcement for perpetuating this pattern of alcohol abuse. Binge-induced anxiety during early (24 h) withdrawal is associated with increased expression of metabotropic glutamate receptor 5 (mGlu5) within the nucleus accumbens shell (AcbSh) of adult male mice, but was unchanged in anxiety-resilient adolescents. Herein, we determined the role of mGlu5 signaling in withdrawal-induced anxiety via pharmacological manipulation using the mGlu5 negative allosteric modulator MTEP and the positive allosteric modulator CDPPB...
January 5, 2018: Drug and Alcohol Dependence
Funda Akkus, Yoan Mihov, Valerie Treyer, Simon M Ametamey, Anass Johayem, Smeralda Senn, Susanne Rösner, Alfred Buck, Gregor Hasler
Glutamate signaling plays a major role in addiction. Preclinical research strongly suggests an implication of G-protein-coupled metabotropic glutamate receptor subtype 5 (mGluR5) in nicotine addiction and alcohol use disorder. In humans, smoking is related to a global reduction in mGluR5 availability. In the present study, we investigated mGluR5 in vivo in patients with alcohol use disorder without the confounding effects of smoking. A total of 14 male subjects with alcohol use disorder and at least a 25-day abstinence and 14 matched male non-smoking healthy controls were included in the study...
January 10, 2018: Translational Psychiatry
Rafael K Varaschin, Nyika A Allen, Martina J Rosenberg, C Fernando Valenzuela, Daniel D Savage
BACKGROUND: We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H3 receptor number and function...
December 5, 2017: Alcoholism, Clinical and Experimental Research
Lucette A Cysique, Lauriane Jugé, Thomas Gates, Michael Tobia, Kirsten Moffat, Bruce J Brew, Caroline Rae
Objective: To assess whether HIV-related brain injury is progressive in persons with suppressed HIV infection. Methods: Seventy-three HIV+ virally suppressed men and 35 HIV- men, screened for psychiatric and alcohol/drug use disorders, underwent neuropsychological evaluation and proton magnetic resonance spectroscopy (1 H-MRS) at baseline and after and 23 ± 5 months.1 H-MRS included brain regions known to be vulnerable to HIV and aging: frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate area (CA)...
January 2018: Neurology® Neuroimmunology & Neuroinflammation
Nazarii Kobyliak, Ludovico Abenavoli, Tetyana Falalyeyeva, Tetyana Beregova
INTRODUCTION AND AIM: Today probiotics have been suggested as a treatment for the prevention of non-alcoholic fatty liver disease (NAFLD). Smectite is a natural silicate that binds to digestive mucous and has the ability to bind endo- and exotoxins. The present study was designed to determine whether probiotics plus smectite is superior to probiotic alone on the monosodium glutamate (MSG) induced NAFLD model in rats. MATERIALS AND METHODS: We included 60 rats divided into 4 groups 15 animals in each...
January 2018: Annals of Hepatology
Mickaël Naassila, Olivier Pierrefiche
The glutamatergic system plays a central role in both the acute and chronic effects of ethanol. Among all the glutamate receptors the ionotropic NMDA receptors are crucial because of their role in synaptic plasticity. A large body of evidences suggests that short-term and long-term effects of ethanol may change synaptic plasticity via an alteration of the expression of the GluN2B subunit, one constitutive element of the NMDA receptor. The present review is focusing on the role of the GluN2B subunit after ethanol exposure during early life (in utero and adolescence) and also at adulthood...
January 6, 2018: Neurochemical Research
Shen Li, Chengkun Jiang, Haitao Wang, Shuang Cong, Mingqian Tan
Foodborne nanoparticles (NPs) have drawn great attention due to human health concerns. This study reports the detection of the presence of fluorescent NPs, about 5 nm, in two of the most popular beverages, Coca-Cola (Coke) and Pepsi-Cola (Pepsi). The NPs contain H, C and O, three elements with a tunable emission and with a quantum yield of 3.3 and 4.3% for Coke and Pepsi, respectively. The presence of sp3-hybridized carbon atoms of alcohols and ethers bonds was confirmed by NMR analysis. The NPs can be taken up by living cells and accumulate within cell membrane and cytoplasm...
December 20, 2017: Nanotoxicology
Daniela Börnigen, Boyu Ren, Robert Pickard, Jingfeng Li, Enver Ozer, Erica M Hartmann, Weihong Xiao, Timothy Tickle, Jennifer Rider, Dirk Gevers, Eric A Franzosa, Mary Ellen Davey, Maura L Gillison, Curtis Huttenhower
Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor oral hygiene are established risk factors. To date, no large-scale case-control studies have considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with oral cancer. We compared the composition, diversity, and function of the oral microbiomes of 121 oral cancer patients to 242 age- and gender-matched controls using a metagenomic multivariate analysis pipeline...
December 15, 2017: Scientific Reports
Jo-Eun Jeong, Je-Keun Rhee, Tae-Min Kim, Su-Min Kwak, Sol-Hee Bang, Hyun Cho, Young-Hoon Cheon, Jung Ah Min, Gil Sang Yoo, Kyudong Kim, Jung-Seok Choi, Sam-Wook Choi, Dai-Jin Kim
The primary aim of this study was to investigate the genetic predisposition of Internet gaming disorder (IGD), and the secondary aim was to compare the results to those of alcohol dependence (AD). Two independent case-control studies were conducted. A total of 30 male participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and 30 sex-matched controls participated in study 1. We designed targeted exome sequencing (TES) to test for 72 candidate genes that have been implicated in the pathogenesis of addiction...
2017: PloS One
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